Endocardium modulates myocardial inotropic response to 5-hydroxytryptamine.

Abstract

The endocardium modulates contractile performance of subjacent myocardium in isolated heart muscle. We investigated the effects of 5-hydroxytryptamine (5-HT, 0.01-30 microM) on isolated cat papillary muscles with or without intact endocardium (+E or -E, respectively). Selective endocardial damage by 1-s immersion in 1% Triton X-100 caused reduction in half-isometric relaxation time (RT1/2) and isometric twitch tension (TT), but not maximum unloaded shortening velocity (Vmax). 5-HT caused reduction in RT1/2 in endocardium-intact but an increase in endocardium-damaged preparations (at 30 microM: -12.1 +/- 1.8%, +E; +5.2 +/- 1.5%, -E). Mean percent increases in TT were greater in endocardium-damaged muscles (at 30 microM: 37.3 +/- 8.6%, +E; 107.3 +/- 19.5%, -E). In the presence of ketanserin (1 microM), 5-HT reduced RT1/2 in endocardium-intact (at 30 microM: -11.9 +/- 1.3%) but not endocardium-damaged muscles (except slightly at 30 microM) and increased TT at 30 microM by 28.7 +/- 4.9% (+E) and 48.9 +/- 15.6% (-E). In the presence of propranolol (1 microM), 5-HT increased RT1/2 (+E and -E) while increasing TT by 23.3 +/- 7.8% (+E) and 43.5 +/- 2.5% (-E). Endocardium did not influence changes in Vmax. Ketanserin (1 microM), but not propranolol (1 microM), markedly diminished endocardial damage induced by 5-HT (greater than or equal to 10 microM). These results suggest a 5-HT-induced endocardium-mediated "inhibitory" effect (causing earlier isometric relaxation) that is not blocked by ketanserin.